Issue 36, 2013
From the journal:

Chemical Communications

Potent and selective HDAC6 inhibitory activity of N-(4-hydroxycarbamoylbenzyl)-1,2,4,9-tetrahydro-3-thia-9-azafluorenes as novel sulfur analogues of Tubastatin A†

Rob De Vreese,a   Tom Verhaeghe,b   Tom Desmetb  and  Matthias D'hooghe*a  

* Corresponding authors

a SynBioC Research Group, Department of Sustainable Organic Chemistry and Technology, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, B-9000 Ghent, Belgium
E-mail: matthias.dhooghe@UGent.be
Fax: +32-9-2646221
Tel: +32-9-2649394

b Centre for Industrial Biotechnology and Biocatalysis, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, B-9000 Ghent, Belgium

Abstract

Eight N-(4-hydroxycarbamoylbenzyl)-1,2,4,9-tetrahydro-3-thia-9-azafluorenes were efficiently prepared as sulfur analogues of Tubastatin A and thus evaluated as new HDAC6 inhibitors. All compounds exhibited potency against HDAC6, and four of them were active in the nanomolar range (IC50 = 1.9–22 nM). Further analysis revealed that the sulfone derivatives (designated as Tubathians) are superior to their non-oxidized sulfide analogues, and the two most active sulfones showed good to excellent HDAC6 selectivity compared to all other HDAC isoform classes.

Graphical abstract: Potent and selective HDAC6 inhibitory activity of N-(4-hydroxycarbamoylbenzyl)-1,2,4,9-tetrahydro-3-thia-9-azafluorenes as novel sulfur analogues of Tubastatin A

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Article information

DOI
https://doi.org/10.1039/C3CC41422A
Article type
Communication
Submitted
24 Feb 2013
Accepted
07 Mar 2013
First published
28 Mar 2013

Chem. Commun., 2013,49, 3775-3777

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Potent and selective HDAC6 inhibitory activity of N-(4-hydroxycarbamoylbenzyl)-1,2,4,9-tetrahydro-3-thia-9-azafluorenes as novel sulfur analogues of Tubastatin A

R. De Vreese, T. Verhaeghe, T. Desmet and M. D'hooghe, Chem. Commun., 2013, 49, 3775 DOI: 10.1039/C3CC41422A

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